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The functional significance of TrkB phosphorylation in the rat nucleus accumbens as a molecular switch of habit formation in drug addiction

Research Project

Project/Area Number 22591257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionKanazawa University

Principal Investigator

TODA Shigenobu  金沢大学, 大学病院, 講師 (00323006)

Co-Investigator(Renkei-kenkyūsha) NAKAHARA Daiichiroh  浜松医科大学, 医学部, 教授 (80128389)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords精神薬理学 / 薬物依存 / 精神薬理 / 脳由来神経栄養因子 / リン酸化 / コカイン / 側坐核 / 可塑性 / TrkB / BDNF
Research Abstract

The phosphorylations of TrkB and ribosomal protein S6 that play crucial roles in activity-dependent protein synthesis contribute to neuronal plasticity and learning/memory. In this study, we examined the effect of cocaine challenge on the important phosphorylation sites of TrkB and rpS6 in the rat nucleus accumbens after repeated saline or cocaine administration. As for TrkB, two distinct phosphorylation sites, one is required for memory acquisition, the other is for memory consolidation, were investigated. Likewise, as for rpS6, two distinct phosphorylation sites, one is mTOR-dependent, other is mTOR-independent, were examined. As a result, we found that the pattern of phosphorylation at each site was so distinctively different between control and chronic-cocaine-treated rats. N-acetylcysteine, which is supposed to restore cocaine-seeking behaviors in rodents did not provide any effect on the phosphorylations in TrkB-mTOT pathway.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (41 results)

All 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (34 results) (of which Invited: 1 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Heroin relapse requires long-term potentiation-like plasticity mediated by NMDA2b-containing receptors2011

    • Author(s)
      Shen H, Moussawi K, Zhow W, Toda S, Kalivas PW
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108 Issue: 48 Pages: 19407-12

    • DOI

      10.1073/pnas.1112052108

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of actin polymerization prevents cocaine-induced changes in spine morphology in the nucleus accumbens2010

    • Author(s)
      S Toda, Haowei Shen, and Peter W Kalivas
    • Journal Title

      Neurotoxicity Research

      Volume: 18 Issue: 3-4 Pages: 410-415

    • DOI

      10.1007/s12640-010-9193-z

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 線条体ドーパミンと精神機能(疾患)2010

    • Author(s)
      戸田重誠
    • Journal Title

      北陸神経精神医学雑誌

      Volume: 24 Pages: 7-17

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Journal Article] Inhibition of actin polymerization prevents cocaine-induced changes in spine morphology in the nucleus accumbens.2010

    • Author(s)
      Shigenobu Toda, Haowei Shen, Peter W Kalivas
    • Journal Title

      Neurotoxicity Research

      Volume: Vol.18 Pages: 410-415

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] The Relevance of Glutamate and Glutathione Homeostasis in Decision-Making and Cocaine Addiction.2012

    • Author(s)
      Shigenobu Toda
    • Organizer
      第35回日本神経科学学会(招待講演)
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Year and Date
      2012-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Shigenobu Toda Cocaine differently affects redox status in the rat nucleus accumbens and dorsal striatum2012

    • Author(s)
      Yoshio Iguchi, Sakurako Kosugi, Yoshio Minabe
    • Organizer
      第35回日本神経科学学会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Year and Date
      2012-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] The Relevance of Glutamate and Glutathione Homeostasis in Decision-Making and Cocaine Addiction2012

    • Author(s)
      Shigenobu Toda
    • Organizer
      第35回日本神経科学学会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Cocaine differently affects redox status in the rat nucleus accumbens and dorsal striatum2012

    • Author(s)
      Yoshio Iguchi, Sakurako kosugi, Yoshio Minabe, Shigenobu Toda
    • Organizer
      第35回日本神経科学学会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dopamine antagonist induces reductions in PSD protein s in the rat nucleus accumbens after repeated cocaine administration2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi, Yoshio Minabe
    • Organizer
      Annual meeting of Society for Neuroscience
    • Place of Presentation
      Convention Center,DC(USA)
    • Year and Date
      2011-11-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Dopamine antagonist induces reductions in PSD protein s in the rat nucleus accumbens after repeated cocaine administration2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi, Yoshio Minabe
    • Organizer
      Annual meeting of Society for Neuroscience
    • Place of Presentation
      Convention Center, DC, USA
    • Year and Date
      2011-11-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] 覚せい剤精神病2011

    • Author(s)
      戸田重誠
    • Organizer
      第21回日本臨床精神神経薬理学会・第41回日本神経薬理学会合同年会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2011-10-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 覚せい剤精神病2011

    • Author(s)
      戸田重誠
    • Organizer
      第21回日本臨床精神神経薬理学会・第41回日本神経薬理学会合同年会
    • Place of Presentation
      京王プラザホテル、東京
    • Year and Date
      2011-10-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Glutamate-independent effects of N-acetylcysteine on synaptic protein turnover in the rat nucleus accumbens after repeated cocaine administration2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi, and Yoshio Minabe
    • Organizer
      第32回内藤コンファレンス「こころの機能と疾患の分子機構」
    • Place of Presentation
      八ヶ岳ロイヤルホテル(山梨)
    • Year and Date
      2011-10-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Glutamate-independent effects of N-acetylcysteine on synaptic protein turnover in the rat nucleus accumbens after repeated cocaine administration2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi, Yoshio Minabe
    • Organizer
      第32回内藤コンファレンス「こころの機能と疾患の分子機構」
    • Place of Presentation
      八ヶ岳ロイヤルホテル、山梨
    • Year and Date
      2011-10-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] コカイン依存における側坐核の役割;ドーパミン、グルタミン酸、そして酸化ストレス2011

    • Author(s)
      戸田重誠
    • Organizer
      アルコール・薬物依存関連学会合同学術総
    • Place of Presentation
      愛知県産業労働センター(愛知)
    • Year and Date
      2011-10-14
    • Related Report
      2012 Final Research Report
  • [Presentation] コカイン依存における側坐核の役割;ドーパミン、グルタミン酸、そして酸化ストレス2011

    • Author(s)
      戸田重誠
    • Organizer
      アルコール・薬物依存関連学会合同学術総会
    • Place of Presentation
      愛知県産業労働センター、愛知
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 側坐核の可塑性と薬物依存;ドーパミン、グルタミン酸に続く因子2011

    • Author(s)
      戸田重誠
    • Organizer
      情動研究会「感覚刺激・薬物による快・不快情動生成機構とその破綻」
    • Place of Presentation
      国立岡崎生理学研究所(愛知)
    • Year and Date
      2011-10-06
    • Related Report
      2012 Final Research Report
  • [Presentation] 側坐核の可塑性と薬物依存;ドーパミン、グルタミン酸に続く因子2011

    • Author(s)
      戸田重誠
    • Organizer
      情動研究会「感覚刺激・薬物による快・不快情動生成機構とその破綻」
    • Place of Presentation
      国立岡崎生理学研究所、愛知
    • Year and Date
      2011-10-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] How do drugs of addiction alter the neuronal functions in the nucleus accumbens:implications of oxidative stress2011

    • Author(s)
      Shigenobu Toda
    • Organizer
      日本神経化学会大会
    • Place of Presentation
      瑠璃光(石川)
    • Year and Date
      2011-09-27
    • Related Report
      2012 Final Research Report
  • [Presentation] How do drugs of addiction alter the neuronal functions in the nucleus accumbens? : implications of oxidative stress2011

    • Author(s)
      Shigenobu Toda
    • Organizer
      日本神経化学会大会
    • Place of Presentation
      瑠璃光、石川
    • Year and Date
      2011-09-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Dopamine antagonist induces reductions in PSD protein s in the rat nucleus accumbens after repeated cocaine administration2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi, Yoshio Minabe
    • Organizer
      日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2011-09-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Dopamine antagonist induces reductions in PSD protein s in the rat nucleus accumbens after repeated cocaine administration2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi, Yoshio Minabe
    • Organizer
      日本神経科学大会
    • Place of Presentation
      パシフィコ横浜、神奈川
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Yoshio Minabe How do drugs of addiction alter the neuronal functions in the rat nucleus accumbens?:implications of oxidative stress. Gordon Research Conference2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi
    • Organizer
      Cathecolamine
    • Place of Presentation
      Bates College, Maine(USA)
    • Year and Date
      2011-08-10
    • Related Report
      2012 Final Research Report
  • [Presentation] How do drugs of addiction alter the neuronal functions in the rat nucleus accumbens? : implications of oxidative stress2011

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Yoshio Iguchi, Yoshio Minabe
    • Organizer
      Gordon Research Conference, "Cathecolamine"
    • Place of Presentation
      Bates College, Maine, USA
    • Year and Date
      2011-08-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Role of PSD structure sustained by action and dopamine in the rat nucleus accumbens after repeated cocaine administration.2010

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Haowei Shen, Yoshio Iguchi, Tetsu Hirosawa, Yoshio Minabe, Peter W Kalivas
    • Organizer
      Annual meeting of society for neuroscience
    • Place of Presentation
      Convention Center, San Diego(USA)
    • Year and Date
      2010-11-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Differential subcellular localization of GluR1 and GluR2 in the nucleus accumbens after repeated cocaine administration;2010

    • Author(s)
      Sakurako Kosugi, Yoshio Iguchi,Tetsu Hirosawa, Yoshio Minabe, Shigenobu Toda
    • Organizer
      implications for the role of glutamatergic tone in protein turnover
    • Place of Presentation
      Convention Center, San Diego(USA)
    • Year and Date
      2010-11-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Role of PSD structure sustained by action and dopamine in the rat nucleus accumbens after repeated cocaine administration.2010

    • Author(s)
      Shieenobu Toda, Sakurako Kosugi, Haowei Shen, Yoshio Iguchi, Tetsu Hirosawa, Yoshio Minabe, Peter W Kalivas
    • Organizer
      Annual meeting of society for neuroscience
    • Place of Presentation
      米国、San Diego
    • Year and Date
      2010-11-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Differential subcellular localization of GluR I and GluR2 in the nucleus accumbens after repeated cocaine administration : implications for the role of glutamatergic tone in protein turnover.2010

    • Author(s)
      Sakurako Kosugi, Yoshio Iguchi, Tetsu Hirosawa, Yoshio Minabe, Sbipenobu Toda
    • Organizer
      Annual meeting of society for neuroscience
    • Place of Presentation
      米国、San Diego
    • Year and Date
      2010-11-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Differential subcellular localization of GluR1 and GluR2 in the nucleus accumbens after repeated cocaine administration;implications for the role of glutamatergic tone in protein turnover2010

    • Author(s)
      Sakurako Kosugi, Yoshio Iguchi,Tetsu Hirosawa, Yoshio Minabe, Shigenobu Toda
    • Organizer
      Molecular and cellular cognitive society
    • Place of Presentation
      Convention Center, San Diego(USA)
    • Year and Date
      2010-11-11
    • Related Report
      2012 Final Research Report
  • [Presentation] Differential subcellular localization of GluR l and GluR2 in the nucleus accumbens after repeated cocaine administration imlications for the role of glutamatergic tone in protein turnover.2010

    • Author(s)
      Sakurako Kosugi, Yoshio Iguchi, Tetsu Hirosawa, Yoshio Minabe, Shieenobu Toda
    • Organizer
      Molecular and cellular cognitive society
    • Place of Presentation
      米国、San Diego
    • Year and Date
      2010-11-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cocaine-induced metaplasticity may be based on the altered balance between protein translation and protein elimination in the rat nucleus accumbens; implications of glutamatergic tone for protein turnover2010

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Haowei Shen, Yoshio Iguchi, Tetsu Hirosawa, Yoshio Minabe, Peter W Kalivas
    • Organizer
      Aquitaine conference on neuroscience
    • Place of Presentation
      Palais des Congres, Archachon(France)
    • Year and Date
      2010-10-14
    • Related Report
      2012 Final Research Report
  • [Presentation] Cocaine-induced metaplasticity may be based on the altered balance betweenprotein translation and protein elimination in the rat nucleus accumbens : implications of glutamatergic tone for protein turnover.2010

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Haowei Shen, Yoshio Iguchi, Tetsu Hirosawa, Yoshio Minabe, Peter W Kalivas
    • Organizer
      Aquitaine conference on neuroscience 2010
    • Place of Presentation
      Archachon, France
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] 物質依存2010

    • Author(s)
      戸田重誠
    • Organizer
      第20回日本臨床精神神経薬理学会・第40回日本神経精神薬理学会 合同年会(招待講演)
    • Place of Presentation
      仙台国際会議場(宮城)
    • Year and Date
      2010-09-14
    • Related Report
      2012 Final Research Report
  • [Presentation] 物質依存2010

    • Author(s)
      戸田重誠
    • Organizer
      第20回日本臨床精神神経薬理学会・第40回日本神経精神薬理学会合同年会
    • Place of Presentation
      仙台国際会議場(官城県)(招待講演)
    • Year and Date
      2010-09-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Subcellular localization of GluR1 and GluR2and their regulatory factors in the nucleus accumbens of repeatedly cocaine-administrated ratsimplications for the role of glutamatergic tone in synaptic protein degradation.2010

    • Author(s)
      Sakurako Kosugi, Yoshio Iguchi, Yoshio Minabe, Shigenobu Toda
    • Organizer
      第33回日本神経科学学会
    • Place of Presentation
      神戸コンベンションセンター(兵庫)
    • Year and Date
      2010-09-04
    • Related Report
      2012 Final Research Report
  • [Presentation] Role of PSD structure sustained by action and tonic dopamine in the rat nucleus accumbens of repeatedly cocaine-administrated rats.2010

    • Author(s)
      Shigenobu Toda, Sakurako Kosugi, Haowei Shen, Yoshio Iguchi, Tetsu Hirosawa,Yoshio Minabe, Peter W Kalivas
    • Organizer
      第33回日本神経科学学会
    • Place of Presentation
      神戸コンベンションセンター(兵庫)
    • Year and Date
      2010-09-04
    • Related Report
      2012 Final Research Report
  • [Presentation] Subcellular localization of GluR l and GluR2and their regulatory factors in the nucleus accumbens of repeatedly cocaine administrated rats : implications for the role of glutamatergic tone in synaptic protein degradation.2010

    • Author(s)
      Sakurako Kosugi, Yoshio Iguchi, Yosbio Minabe, Sbieenobu Toda
    • Organizer
      第33回日本神経科学学会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of PSD structure sustained by action and tonic dopamine in the ratnucleus accumbens of repeatedly cocaine administrated rats.2010

    • Author(s)
      Shieenobu Toda, Sakurako Kosugi, Haowei Shen, YoshioIguchi, Tetsu Hirosawa, Yoshio Minabe, Peter W Kalivas
    • Organizer
      第33回日本神経科学学会
    • Place of Presentation
      神戸コンベンションセンター (兵庫県)
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Book] 「線条体と依存症」Brain and Nerve2012

    • Author(s)
      戸田重誠
    • Total Pages
      64
    • Publisher
      医学書院
    • Related Report
      2012 Final Research Report
  • [Book] Brain and Nerve,64: 線条体と依存症2012

    • Author(s)
      戸田重誠
    • Total Pages
      7
    • Publisher
      医学書院
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://web.kanazawa-u.ac.jp/~med20/index.htm

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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